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Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs

dc.contributor.authorDéjardin, Théophile
dc.contributor.authorCarollo, Pietro Salvatore
dc.contributor.authorSipieter, François
dc.contributor.authorDavidson, Patricia M
dc.contributor.authorSeiler, Cynthia
dc.contributor.authorCuvelier, Damien
dc.contributor.authorCadot, Bruno
dc.contributor.authorSykes, Cecile
dc.contributor.authorGomes, Edgar
dc.contributor.authorBorghi, Nicolas
dc.date.accessioned2021-04-09T15:56:24Z
dc.date.available2021-04-09T15:56:24Z
dc.date.issued2020
dc.description© 2020 Déjardin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).pt_PT
dc.description.abstractLINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in a nesprin protein of the LINC complex of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic, and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that nesprin experiences tension generated by the cytoskeleton and acts as a mechanical sensor of cell packing. Moreover, nesprin discriminates between inductions of partial and complete epithelial-mesenchymal transitions. We identify the implicated mechanisms, which involve α-catenin capture at the nuclear envelope by nesprin upon its relaxation, thereby regulating β-catenin transcription. Our data thus implicate LINC complex proteins as mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the epithelial-mesenchymal transition program.pt_PT
dc.description.sponsorshipThis material is based on work supported by the Centre national de la recherche scientifique (CNRS), Agence nationale de la recherche (ANR; grants ANR-13-JSV5-0007 and ANR-14-CE09-0006), France BioImaging (ANR-10-INBS-04), la Ligue contre le Cancer (REMX17751 to P.M. Davidson), and the Fondation ARC pour la Recherche sur le Cancer (PDF20161205227 to P.M. Davidson). P.S. Carollo has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation (Marie Skłodowska-Curie grant agreement 665850-INSPIRE) and acknowledges the Ecole Doctorale Frontières de l'Innovation en Recherche et Éducation (FIRE) Programme Bettencourt. E.R. Gomes was supported by a European Research Council consolidator grant (617676).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Cell Biol. 2020 Oct 5;219(10):e201908036pt_PT
dc.identifier.doi10.1083/jcb.201908036pt_PT
dc.identifier.eissn1540-8140
dc.identifier.issn0021-9525
dc.identifier.urihttp://hdl.handle.net/10451/47321
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRockefeller University Presspt_PT
dc.relationPositioning the nucleus for cell migration and muscle fiber function
dc.relationINterdiSciPlinarity and excellence for doctoral training of International REsearchers in Paris
dc.relation.publisherversionhttps://rupress.org/jcbpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.titleNesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePositioning the nucleus for cell migration and muscle fiber function
oaire.awardTitleINterdiSciPlinarity and excellence for doctoral training of International REsearchers in Paris
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/617676/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/665850/EU
oaire.citation.issue10pt_PT
oaire.citation.titleThe Journal of Cell Biologypt_PT
oaire.citation.volume219pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamH2020
person.familyNameGomes
person.givenNameEdgar
person.identifier.ciencia-id6215-9445-3042
person.identifier.orcid0000-0002-6941-4872
person.identifier.ridD-9000-2015
person.identifier.scopus-author-id7102464212
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationbd5022e4-63ff-4d9e-b4f4-3fc163836720
relation.isAuthorOfPublication.latestForDiscoverybd5022e4-63ff-4d9e-b4f4-3fc163836720
relation.isProjectOfPublication68294341-d459-4699-9501-00b1ee72d009
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